Oral GLP-1 drug shows promise for adults with diabetes and obesity

Orforglipron , an investigative and oral GLP-1 drug, appears to enable adults with obesity and Type 2 diabetes to achieve significantly more weight loss and improvement in blood sugar levels than a placebo.

Researchers from the ATTAIN-2 trial reported their findings on Nov. 20, 2025 in The Lancet.

“We know it is harder for individuals with diabetes to lose weight. It is exciting to have an oral medication that provides double-digit weight loss, which on average was 23 lbs. Once FDA approved, orforglipron is scheduled to be available in 2026 at a significantly decreased cost compared to current injectables. This could position it to be the ‘metformin’ of obesity and become widely covered by insurance plans, opening the door to treatment for all,” said Deborah Horn, DO, MPH, professor and director of obesity medicine at McGovern Medical School at UTHealth Houston and principal author of the study.

Orforglipron stimulates insulin release, reduces glucagon secretion, lowers blood sugar and helps control appetite. No refrigeration is needed.

The investigators conducted the 72-week, phase 3, double-blind, placebo-controlled trial across 136 sites in ten countries.

The primary endpoint was the mean percent change in bodyweight from baseline to week 72.

The investigators enrolled 1613 subjects (757 female) and randomized them, after a dose escalation phase, to receive orforglipron 6 mg (n=329), 12 mg (n=332), 36 mg (n=322), or placebo (n=630), as an adjunct to lifestyle modification.

Of the total group, 1444 (89·5%) completed the 72-week study.

At endpoint, subjects treated with up to 6 mg of orforglipron averaged a weight loss of 5.5%, those who received 12 mg averaged 7.8%, and those who received 36 mg averaged 10.5%.

The placebo group averaged just 2.2% in weight loss.

Orforglipron treatment significantly improved blood sugar and caused only mild to moderate gastrointestinal side effects.

The authors reported, “All prespecified weight and cardiometabolic measures including HbA_1c statistically significantly improved with orforglipron. Treatment discontinuations due to adverse events (mainly gastrointestinal-related) were higher for orforglipron (6·1–9·9%) versus placebo (4·1%). The most common adverse events with orforglipron were mild-to-moderate gastrointestinal events, predominantly occurring during dose escalation.”

The authors concluded, “In adults with obesity or overweight and type 2 diabetes, statistically superior reduction in bodyweight compared with placebo was demonstrated by once-daily orforglipron as an adjunct to lifestyle modification, with a safety profile similar to other GLP-1 receptor agonists.”

Horn added, “The opportunity for an oral GLP-1 medication with highly effective weight loss that is simpler to take may provide increased access and opportunities for better health for our patients with obesity and diabetes.”